Abstract 2773
Background
Etoposide toniribate (also known as EDO-S7.1, and previously known as CAP7.1), a novel topoisomerase II inhibitor, is activated in the presence of carboxylesterases. In specific tumor cell lines, it was found to be more active than etoposide, with in vivo activity demonstrated in several drug-resistant tumor models. Anti-tumor activity was confirmed in a Phase II randomized study in patients (pts) with relapsed BTC.
Methods
Pts with BTC and disease progression after ≥1 line of chemotherapy were randomized 1:1 to 3-week cycles of etoposide toniribate (200 or 150mg/m2; iv on days 1–5), or best supportive care (BSC). Pts who progressed on BSC crossed over to receive etoposide toniribate. Efficacy data collected after crossover were evaluated separately as part of this post-hoc exploratory analysis.
Results
The per protocol analysis set included 19 pts: 10 pts were randomized to BSC, and crossed over to etoposide toniribate after disease progression, 9 pts were randomized directly to the etoposide toniribate treatment arm. Treatment after crossover from BSC to etoposide toniribate was associated with a trend for improved disease control: n/N (%; 95% CI) 4/10 (40%; 12.2, 73.8) vs 2/10 (20%; 2.5, 55.6), with tumor control achieved in 4/10 patients (1 pt partial response, 3 pts stable disease). Risk of disease progression was 2.33 times higher during BSC treatment vs after crossover to etoposide toniribate. Crossover from BSC to etoposide toniribate was associated with a trend for prolonged median PFS (39 vs 50 days). Median OS for pooled etoposide toniribate and crossover pts was 145 (59, 243) days, estimated 1-year OS 14.1%. Median (95% CI) OS for etoposide toniribate vs crossover pts was 180 (43, 468) vs 83 (11, 243) days, HR 0.39 (0.13, 1.18), estimated 1-year OS 29.6% (5.2%, 60.7%) vs 0%.
Conclusions
This post-hoc analysis provides further evidence for the efficacy of etoposide toniribate and suggests that early initiation in pts with advanced BTC may offer a potential survival benefit. The efficacy of etoposide toniribate will be further investigated in a planned phase III study. Funding: CellAct Pharm GmbH and Mundipharma EDO GmbH.
Clinical trial identification
NCT02094560.
Editorial acknowledgement
Sarah Birch, PhD, at Makara Health Communications Ltd, UK, funded by Mundibiopharma Ltd.
Legal entity responsible for the study
CellAct Pharma GmbH.
Funding
CellAct Pharma GmbH, Mundipharma EDO GmbH.
Disclosure
U. Pape: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Shire; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen. S. Kasper: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Research grant / Funding (self): Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: Lilly. J. Meiler: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi/Aventis. M. Sinn: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self): Leo Pharma; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Incyte; Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Servier; Research grant / Funding (self): Taiho Pharmaceutical. H. Jansen: Advisory / Consultancy: CellAct Pharma. T. Mehrling: Leadership role, Full / Part-time employment: Mundipharma EDO. K. Hilgier: Advisory / Consultancy: Mundipharma EDO. I. Wagner: Full / Part-time employment: Mundipharma EDO. N. Utku: Honoraria (self), Advisory / Consultancy, Leadership role, Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: CellAct Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Mundipharma EDO; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
5629 - Outcome of triple negative inflammatory breast cancers (TNIBC) treated with dose dense neoadjuvant epirubicin cyclophosphmide, prognostic impact of pre and post neoadjuvant chemotherapy (NAC) tumor infiltrating lymphocytes (TIL) and post NAC lymphovascular invasion
Presenter: Luca Campedel
Session: Poster Display session 2
Resources:
Abstract
5792 - A novel PET parameter for cancer stem cell metabolism: early prediction of chemosensitivity to neoadjuvant chemotherapy in locally advanced breast cancer
Presenter: Chanwoo Kim
Session: Poster Display session 2
Resources:
Abstract
3728 - Using nodal ratio to predict recurrence in patients with 4 or more positive lymph nodes early stage breast cancer
Presenter: Besma Graja
Session: Poster Display session 2
Resources:
Abstract
3395 - Re-sentinel node biopsy for local recurrence after breast-conserving surgery
Presenter: Yuka Matsubara
Session: Poster Display session 2
Resources:
Abstract
4302 - Assessment of prognostic and therapeutic factors in men with breast cancer
Presenter: Daniel Herrero Rivera
Session: Poster Display session 2
Resources:
Abstract
4263 - Genomic Profiling of Chinese Breast Cancer Patients
Presenter: Zhonghua Tao
Session: Poster Display session 2
Resources:
Abstract
2406 - Genome copy number alteration burden represents predictor of response in long-term, never relapse exceptional responders of trastuzumab-treated HER2+ metastatic breast cancer
Presenter: Naomi Walsh
Session: Poster Display session 2
Resources:
Abstract
2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations
Presenter: Nicholas C. Turner
Session: Poster Display session 2
Resources:
Abstract
4499 - FGFR1 and CCND1 gene amplifications are associated with breast cancer resistance to aromatase inhibitors
Presenter: Evgeny Imyanitov
Session: Poster Display session 2
Resources:
Abstract
4110 - Clinicopathologic features of BRCA mutated breast cancer patients: Hacettepe Experience
Presenter: Sercan Aksoy
Session: Poster Display session 2
Resources:
Abstract